Impact of an ROX index-guided intubation strategy on mortality in patients receiving high-flow nasal cannula: a target trial emulation.

Authors

Ryohei Yamamoto, Takeshi Tohyama, Ahram Han, Norman Pedersen, Kerollos Nashat Wanis, Joseph Byers, Leo Anthony Celi

Published in

Journal of intensive care. Volume 14. Issue 1. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

The ROX index (the ratio of peripheral oxygen saturation to the fraction of inspired oxygen, divided by respiratory rate) has been validated to predict high-flow nasal cannula (HFNC) failure, but whether acting on ROX to guide the timing of intubation improves patient outcomes is unknown. We estimated the per-protocol effect of ROX-guided strategies versus usual care on mortality after HFNC initiation.
We emulated target trials using Medical Information Mart for Intensive Care IV (MIMIC-IV) electronic health record data. Adults initiated on HFNC within 7 days of intensive care unit (ICU) admission were eligible. Strategies were usual care or intubation within 2 h after ROX first fell below 3.85, 4.88, or time-varying thresholds (2.85 for hours 1-5, 3.47 for hours 6-11, and 3.85 from hour 12). We used clone-censor-weighting with pooled logistic regression, adjusted for baseline and time-varying covariates, to estimate 30-day mortality.
We included 1,651 adults (median age, 66 years; women, 41%). Estimated 30-day mortality under usual care was 26.9% (95% CI 24.7-29.2). ROX < 3.85: 20.5% (95% CI 17.1-24.1; risk difference [RD], -6.5 percentage points [95% CI -9.1 to -3.8]; risk ratio [RR], 0.76 [95% CI 0.66-0.86]). ROX < 4.88: 19.8% (95% CI 16.3-24.0; RD, -7.1 percentage points [95% CI -10.3 to -3.5]; RR, 0.74 [95% CI 0.62-0.87]). Time-varying ROX: 21.3% (95% CI 18.5-24.3; RD, -5.6 percentage points [95% CI -7.9 to -3.4]; RR, 0.79 [95% CI 0.70-0.87]).
ROX-guided intubation strategies were associated with lower 30-day mortality than usual care. These findings are hypothesis-generating and support prospective evaluation of the ROX index applied as a decision policy rather than as a prediction score alone; they should not be used to guide intubation decisions at present.

PMID:
42698089
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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